SAFETY CONSIDERATIONS1: 

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA. Patients treated with HUMIRA also may be at risk for other serious adverse reactions including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.

REVEAL Study

Indication1
HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

REVEAL: Trial Study Design1,2

Primary efficacy endpoints1

  • Proportion of patients achieving PASI 75 response relative to baseline at week 16
  • Proportion of patients achieving clear or minimal disease on the 6-point PGA scale at week 16

aAfter 80 mg at week 0 and 40 mg at week 1.
bAfter 80 mg at week 16 and 40 mg at week 17.


Study design REVEAL was a randomized, double-blind, placebo-controlled study that evaluated 1212 patients with chronic plaque psoriasis with ≥10% BSA involvement, PGA of at least moderate disease severity, and PASI ≥12 within 3 treatment periods. In period A, patients were randomized to receive HUMIRA at an initial dose of 80 mg at week 0 followed by 40 mg EOW starting at week 1, or placebo. After 16 weeks of therapy, patients who achieved at least a PASI 75 response at week 16 entered period B and received open-label HUMIRA 40 mg EOW. After 17 weeks of open-label therapy, patients who maintained at least a PASI 75 response at week 33 and were originally randomized to HUMIRA in period A were rerandomized in period C to receive HUMIRA 40 mg EOW or placebo for an additional 19 weeks.

EOW=every other week; PASI=Psoriasis Area and Severity Index; BSA=body surface area; PGA=Physician's Global Assessment.

REVEAL: PASI Improvement and PGA Score at Week 161-3

The analysis above is of the intention-to-treat (ITT) population, using nonresponder imputation (NRI) methodology. Patients who had missing data were counted as nonresponders for between-treatment comparison.2,3
  • 71% of HUMIRA-treated patients achieved PASI 75 at week 16 of the REVEAL trial vs 7% of placebo-treated patients (P <0.001)1,2
  • A PGA score* of clear or minimal was achieved in 62% of HUMIRA-treated patients at week 16 vs 4% of placebo-treated patients (P <0.001)1,3

*PGA score of clear indicates no plaque elevation, no scale, plus or minus hyperpigmentation or diffuse pink or red coloration. PGA score of minimal indicates possible but difficult to ascertain whether there is slight elevation of plaque above normal skin, plus or minus surface dryness with some white coloration, plus or minus up to red coloration.1


Example of PASI 75 improvement at week 16

PASI 75 Before and After Images

Actual clinical trial patient results. Individual results may vary.


  • 82% of HUMIRA-treated patients achieved PASI 50 at week 16 vs 15% of placebo-treated patients in the REVEAL trial3

Example of PASI 50 improvement at week 16

PASI 65 Before and After Images

Actual clinical trial patient results. Individual results may vary.


  • 45% of HUMIRA-treated patients achieved PASI 90 at week 16 vs 2% of placebo-treated patients in the REVEAL trial2

Example of PASI 90 improvement at week 16

Before and After Images

Actual clinical trial patient results. Individual results may vary.


Maintained efficacy through week 521

HUMIRA-treated patients who maintained PASI 75 were re-randomized to HUMIRA (n=250) or placebo (n=240) at week 33

  • 79% of HUMIRA-treated patients maintained PASI 75 response at week 52 vs 43% of patients re-randomized to placebo
  • 68% of HUMIRA-treated patients maintained a PGA of clear or minimal disease at week 52 vs 28% of patients re-randomized to placebo

IMPORTANT SAFETY INFORMATION1

SERIOUS INFECTIONS

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

HUMIRA should be discontinued if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before HUMIRA use and during therapy. Treatment for latent TB should be initiated prior to HUMIRA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

The risks and benefits of treatment with HUMIRA should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

  • Do not start HUMIRA in patients with an active infection, including localized infections.
  • Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
  • Exercise caution in patients with chronic or recurrent infection or with underlying conditions which may predispose them to infection, patients who have been exposed to TB, patients with a history of opportunistic infection, or patients who have resided or traveled in regions where TB or mycoses are endemic.
  • Patients who develop a new infection should undergo a prompt and complete diagnostic workup, and appropriate antimicrobial therapy should be initiated.
  • Drug interactions with biologic products: Concurrent use of anakinra or abatacept with HUMIRA is not recommended, as the combination of anakinra or abatacept with TNF blockers has been associated with an increased risk of serious infections. This risk has also been observed with rheumatoid arthritis patients treated with rituximab who received subsequent treatment with a TNF blocker.

MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases has occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

  • The risks and benefits of HUMIRA treatment should be considered prior to initiating or continuing therapy in a patient with known malignancy.
  • More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials.
  • Non-melanoma skin cancer (NMSC) has been reported during clinical trials for HUMIRA-treated patients. All patients, particularly those with history of prolonged immunosuppressant or PUVA therapy, should be examined for the presence of NMSC prior to and during treatment with HUMIRA.
  • In HUMIRA clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.
  • Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use.
  • Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.

HYPERSENSITIVITY

  • Anaphylaxis and angioneurotic edema have been reported rarely following HUMIRA administration.
  • If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.

HEPATITIS B VIRUS REACTIVATION

  • Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
  • Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating TNF blocker therapy.
  • Exercise caution in patients who are carriers of HBV and monitor them during and after treatment with HUMIRA.
  • Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation.
  • Exercise caution when considering resumption of HUMIRA therapy after appropriate treatment for HBV.

NEUROLOGIC REACTIONS

  • TNF blockers, including HUMIRA, have been associated in rare cases with new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.
  • Exercise caution when considering HUMIRA for patients with these disorders.

HEMATOLOGIC REACTIONS

  • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g. thrombocytopenia, leukopenia) has been infrequently reported with HUMIRA.
  • Consider stopping HUMIRA in patients with significant hematologic abnormalities.

CONGESTIVE HEART FAILURE

  • Worsening or new onset congestive heart failure (CHF) may occur.
  • Exercise caution in patients with CHF and monitor them carefully.

AUTOIMMUNITY

  • Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome.
  • Discontinue treatment if symptoms of a lupus-like syndrome develop.

IMMUNIZATIONS

  • Patients on HUMIRA should not receive live vaccines.
  • It is recommended that juvenile idiopathic arthritis patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HUMIRA therapy.

ADVERSE REACTIONS

  • The most common adverse reactions in HUMIRA clinical trials (incidence >10%) were: infections (e.g. upper respiratory, sinusitis), injection site reactions, headache, and rash.

INDICATIONS1

  • Rheumatoid Arthritis: HUMIRA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
  • Juvenile Idiopathic Arthritis: HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients 4 years of age and older.
  • Psoriatic Arthritis: HUMIRA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
  • Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
  • Crohn's Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
  • Plaque Psoriasis: HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

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References:
1. HUMIRA Injection [package insert]. North Chicago, IL: Abbott Laboratories. 2. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106-115. 3. Data on file, Abbott Laboratories.

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